Transcriptomic analysis of Androgen-dependent Human Prostate Cancer LNCaP Cells and its Tumor Xenograft to elucidate the components and mechanisms contributed by tumor environment

Authors: YU, LU - University Of Maryland; Li, Robert; HUANG, HAIQIU - University Of Maryland; Pham, Quynhchi; YU, LIANGLI - University Of Maryland; Wang, Thomas - Tom

Submitted to: Nutrients
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 3/11/2021
Publication Date: 3/19/2021
Citation: Yu, L., Li, R.W., Huang, H., Pham, Q., Yu, L., Wang, T.T.Y. 2021. Transcriptomic analysis of LNCaP tumor xenograft to elucidate the components and mechanisms contributed by tumor environment as targets for dietary prostate cancer prevention studies. Nutrients. 13(3):1000. https://doi.org/10.3390/nu13031000.
DOI: https://doi.org/10.3390/nu13031000

Interpretive Summary: Cancer prevention through the diet requires the understanding of how the diet works mechanistically; and rodent models are often used for this purpose. The LNCaP athymic xenograft model has been widely used to allow researchers to examine the effects and mechanisms of experimental treatments such as diet and cancer preventive and therapeutic compounds on prostate cancer. However, the biological characteristics of human LNCaP cells before/after implanting in an athymic mouse and its relevance to clinical human prostate outcomes remain unclear, and may dictate interpretation of biological efficacies/mechanisms of experimental treatments. In this study, transcriptome profiles and pathways of human prostate LNCaP cells before (in vitro) and after (in vivo) implanting into a xenograft mouse were compared using RNA-sequencing technology (RNA-seq), followed by bioinformatic analysis. A shift from androgen-responsive to androgen non-responsive status was observed when comparing the LNCaP xenograft tumor to culture cells. The sndrogen receptor, as well as the aryl-hydrocarbon pathway, were found to be inhibited and IL-1 mediated pathways contributed to these changes. Coupled with in-vitro experiments modeling for androgen exposure, cell-matrix interaction, inflammation and hypoxia, we identified specific mechanisms that may contribute to the observed changes in genes and pathways. Our results provide critical baseline transcriptomic information for the tumor xenograft model and the tumor environments that might be associated with regulating the progression of the xenograft tumor which may influence the interpretation of experimental treatments. This study provides novel information on a rodent model system widely used in our diet, cancer prevention study. The information will benefit basic, translational scientists who use the model to query mechanistic aspects of cancer preventive bioactives.

Technical Abstract: The LNCaP athymic xenograft model has been widely used to allow researchers to examine the effects and mechanisms of experimental treatments such as diet and cancer preventive and therapeutic compounds on prostate cancer. However, the biological characteristics of human LNCaP cells before/after implanting in athymic mouse and its relevance to clinical human prostate outcomes remain unclear and may dictate interpretation of biological efficacies/mechanisms of experimental treatments. In this study, transcriptome profiles and pathways of human prostate LNCaP cells before (in vitro) and after (in vivo) implanting into a xenograft mouse were compared using RNA-sequencing technology (RNA-seq), followed by bioinformatic analysis. A shift from androgen-responsive to androgen non-responsive status was observed when comparing the LNCaP xenograft tumor to culture cells. Androgen receptors, as well as an aryl-hydrocarbon pathway, were found to be inhibited and IL-1 mediated pathways contributed to these changes. Coupled with in-vitro experiments modeling for androgen exposure, cell-matrix interaction, inflammation and hypoxia, we identified specific mechanisms that may contribute to the observed changes in genes and pathways. Our results provide critical baseline transcriptomic information for a tumor xenograft model and the tumor environments that might be associated with regulating the progression of a xenograft tumor which may influence interpretation of experimental treatments.